Shulyak N. Development and Validation of Methods for the Analysis of Atorvastatin and Lisinopril in Medicinal Products

The thesis presents an experimental study of the development of spectrophotometric and chromatographic methods for the determination of atorvastatin and lisinopril in substances and medicinal products. UV-spectrophotometric methods for the determination of atorvastatin calcium and lisinopril in mono-preparations have been developed and validated. Spectrophotometric methods for the quantitative determination of lisinopril in the composition of ready-made dosage forms by the ninhydrin reaction and the reaction with copper (II) sulfate have been developed and validated. It was considered the possibility of applying the method of differential spectrophotometry by reaction with bromophenol blue (BPB) using the maximum absorbance of the reaction product at a wavelength of 594 nm. Chromatographic conditions have been proposed and HPLC method has been developed for the quantitative determination of atorvastatin calcium and its impurities in tablets. Chromatographic columns Shim-Pack XR-ODS II (75 mm x 3 mm, 2.2 μm) and Agilent Poroshell C18ec (100 mm x 4.6 mm, 2.7 μm) have demonstrated excellent results in the separation of atorvastatin and its impurities. The developed validated method for determining atorvastatin calcium and its impurities in tablets is more environmentally friendly than the pharmacopoeia and all other previously published methods for determining atorvastatin calcium impurities, express for routine analyzes in quality control laboratories of pharmaceutical companies. Chromatographic methods for the simultaneous determination of atorvastatin calcium and lisinopril in a binary mixture and medicinal products using Purospher C8 STAR, Zorbax C8 Rx, LiChrosorb C8, Waters Spherisorb ODS1 chromatographic columns have been developed and validated. A methodology for the development of HPLC method for the simultaneous quantitative determination of two APIs with significant differences in physicochemical properties is proposed. It can be concluded that the developed spectrophotometric methods for the determination of lisinopril and atorvastatin in tablets for use in order to conduct the “Dissolution” test are correct, express and available. Novelty of developments is confirmed by patents of Ukraine for a useful model.